“I cannot in good conscience vote for the Graham-Cassidy proposal. I believe we could do better working together, Republicans and Democrats, and have not yet really tried," McCain said in a statement.

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McCain's announcement leaves GOP leadership with no room for error. They need 50 GOP senators to support the legislation, which would let Vice President Mike Pence break a tie.

The Arizona Republican previously dealt a death blow to the Senate GOP’s “skinny repeal” bill, casting a surprise late-night “no” vote against the bill in July.

Kimmel has become the public face of the opposition against the Graham-Cassidy bill, devoting much of his monologues in recent days to diving into the battle over the legislation.

On Tuesday, Kimmel accused Cassidy of neglecting to fulfill his previous promise to only support a bill that would pass the “Jimmy Kimmel test.”

“Not only did Bill Cassidy fail the Jimmy Kimmel test, he failed the Bill Cassidy test. He failed his own test,” Kimmel said.

Cassidy fired back at Kimmel, saying the comedian “just doesn’t understand” the bill. Kimmel hit back in turn, later rippingCassidy for suggesting he didn’t understand the legislation.

"Oh I get it, I don't understand it because I'm a talk show host," Kimmel said during his opening monologue late Wednesday. "Then help me out. Which part don't I understand? The part where you cut $243 billion dollars from federal health-care assistance? Am I not understanding the part where states would let insurance companies price you out of coverage for having pre-existing conditions?"

“Could it be, Sen. Cassidy, that the problem is that I do understand and you got caught with your G-O-Penis out. Is that possible?” Kimmel asked.

In May, Kimmel delivered an impassioned plea in favor of ObamaCare after revealing his son was born with a heart defect that required emergency open-heart surgery.

“Let’s stop with the nonsense. This isn’t football. There are no teams,” Kimmel said at the time. “We are the team. It’s the United States. Don’t let their partisan squabbles divide us on something every decent person wants.”

“No parent should ever have to decide if they can afford to save their child’s life. It just shouldn’t happen. Not here.”